On January 18, 2022 ADC Therapeutics SA (NYSE: ADCT), a commercial-stage biotechnology company improving the lives of those affected by cancer with its next-generation, targeted antibody drug conjugates (ADCs) for patients with hematologic malignancies and solid tumors, reported it has entered an exclusive license agreement with Mitsubishi Tanabe Pharma Corporation (MTPC) for the development and commercialization of ZYNLONTA (loncastuximab tesirine-lpyl) for all hematologic and solid tumor indications in Japan (Press release, ADC Therapeutics, JAN 18, 2022, View Source [SID1234605512]).

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Under the terms of the agreement, ADC Therapeutics will receive an upfront payment of $30 million and up to an additional $205 million in milestones if certain development and commercial events are achieved. ADC Therapeutics will also receive royalties ranging in percentage from the high teens to the low twenties based on net sales of the product in Japan. MTPC will conduct clinical studies of ZYNLONTA in Japan and will have the right to participate in any global clinical studies of the product by bearing a portion of the costs of the study.

In April 2021, the U.S. Food and Drug Administration (FDA) granted accelerated approval to ZYNLONTA as the first and only CD19-targeted ADC as a single-agent treatment for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy. A Marketing Authorization Application (MAA) for ZYNLONTA has been validated by the European Medicines Agency (EMA) and is under review by the EMA’s Committee for Medicinal Products for Human Use (CHMP). ZYNLONTA has also received Orphan Drug designation in Europe for DLBCL. In addition, Overland ADCT BioPharma, a joint venture formed by Overland Pharmaceuticals and ADC Therapeutics, is working to develop and commercialize ZYNLONTA in greater China and Singapore. Overland ADCT BioPharma is now conducting a pivotal Phase 2 clinical trial of ZYNLONTA in relapsed or refractory DLBCL in China, which is intended to support the anticipated registration of ZYNLONTA in China.

About ZYNLONTA (loncastuximab tesirine-lpyl)

ZYNLONTA is a CD19-directed antibody drug conjugate (ADC). Once bound to a CD19-expressing cell, ZYNLONTA is internalized by the cell, where enzymes release a pyrrolobenzodiazepine (PBD) payload. The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms. This ultimately results in cell cycle arrest and tumor cell death.

The U.S. Food and Drug Administration (FDA) has approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including DLBCL not otherwise specified, DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma. The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with difficult-to-treat disease, including patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, patients with double/triple hit genetics and patients who had stem cell transplant and CAR-T therapy prior to their treatment with ZYNLONTA. This indication is approved by the FDA under accelerated approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ZYNLONTA is also being evaluated as a therapeutic option in combination studies in other B-cell malignancies and earlier lines of therapy.

On January 17, 2022 Shanghai Huaota Biopharmaceutical Co., Ltd. (hereinafter referred to as "Huaota") reported FDA approval for the anti-PD-L1/TIGIT bispecific antibody (project code HB0036), which was independently developed by the company, to enter clinical trial (Press release, Huabo Biopharm, JAN 17, 2022, View Source [SID1234656056]). This is also the second bispecific antibody project of Huaota that has been approved by the FDA to enter clinic trial (the first is a PD-L1/VEGF bispecific antibody project). HB0036 is the world’s first FDA-approved bispecific antibody targeting two key immune checkpoints -PD-L1 and TIGIT. Dr. Xiangyang Zhu, General Manager of Huaota, expressed his excitement about this project. He stated that HB0036 has excellent CMC properties and excellent anti-tumour effect in preclinical studies. In light of the exciting clinical results of the combination therapy of Atezolizumab and Tiragolumab reported by Roche, he anticipates that HB0036 could bring enhanced benefits to the patients and hopes that clinical study with HB0036 could be launched as soon as possible.

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HB0036 is the second bispecific antibody developed by Huaota. It binds to PD-L1 and TIGIT with high specificity and affinity. It has strong anti-tumor effect by blocking both PD-1/PD-L1 and TIGIT/CD155 signaling pathways, ameliorating the immunosuppressive effects mediated by these two signaling pathways and reactivating cytotoxic T lymphocytes and NK cells against tumor cells. In addition, since HB0036 retains the ADCC effect mediated by PD-L1 and TIGIT, it can kill tumor cells and Treg cells, and further enhance the anti-tumor effect.

Preclinical studies have shown that the antitumor effect of HB0036 is better than that of the single drug, and is comparable to the combinational use of two separate antibody drugs. Preclinical pharmacokinetic results in non-human primates showed that HB0036 has linear pharmacokinetic characteristics, long half-life and satisfactory pharmacokinetic properties. Toxicological studies showed that HB0036 is safe and well tolerated, and has great potential to become a new generation of tumor therapy drugs.

There is currently no drug targeting both pathways on the market worldwide. The most advanced competitor drug is the combination of anti-PD-L1 monoclonal antibody Atezolizumab and anti-TIGIT monoclonal antibody Tiragolumab by Roche. In January 2021, the FDA granted Roche’s Atezolizumab in combination with Tiragolumab the Breakthrough Therapy Drug (BTD) designation for first-line treatment of NSCLC. Many companies are also conducting research on PD-1/TIGIT bispecific antibody.

On January 17, 2022 Tyligand Bioscience, a clinical-stage biotechnology company developing innovative small-molecule therapeutics against drug resistant cancers, reported that its investigational new drug (IND) application of TSN084 has been approved by China’s National Medical Products Administration (NMPA) (Press release, Tyligand Bioscience, JAN 17, 2022, View Source [SID1234644991]).

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TSN084 is a first-in-class phosphorylation inhibitor targeting CDK8/19 and several other kinases implicated in tumorigenesis and immune evasions. Phase I enrollment will be conducted at the Cancer Hospital of the Chinese Academy of Medical Sciences and other clinical centers. In Oct 2021, the company has received IND approval from the US FDA for the experimental drug and dose escalation studies are expected to commence soon.

Dr. Tony Zhang, cofounder and CEO of Tyligand Bioscience, commented, "We are excited about this important milestone and the potential of TSN084 for helping patients with tough to treat tumors. Accomplishing this goal is testimonial to the quality and speed of the Tyligand team at transforming novel molecules into quality drug candidates. It is an important step toward testing our approach of selective and simultaneous inhibition of multiple factors responsible for the major hallmarks of cancer."

On January 17, 2022 Aclys Bio Corp ("Aclys"), a company discovering and developing precision biologics for the treatment of cancer, earlier this month reported a new exclusive research and commercial license option agreement with Genmab A/S (Nasdaq: GMAB), an international biotech company specializing in the creation and development of differentiated antibody therapeutics for the treatment of cancer (Press release, Virtici, JAN 17, 2022, View Source [SID1234608857]).

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Under the terms of the agreement, Genmab secures exclusive rights to Aclys antibodies (specific to an undisclosed target) for further research in conjunction with Genmab’s proprietary platforms. Genmab is also granted the option to advance development and commercialization of resulting products.

Aclys has built a broad range of antibodies using its PILA platform to create targeted therapeutics for solid tumors. The agreement with Genmab recognizes the capability of the Aclys PILA platform to identify novel precision targets.

"We have differentiated, high value targets, unique antibody engineering capabilities, and a team that has delivered some of the most valuable monoclonal antibodies currently in development.", said Dr. Tony Cooper, Aclys Cofounder and CEO. "This agreement with Genmab is integral to advancing our goal of delivering life-saving therapies to patients." Aclys is a leader in the emerging field of precision immune medicine. Aclys utilizes a proprietary set of patient molecular data to select differentiated targets and create precision biologics with the safety profile and response rates only achievable with precision biologics.

On January 18, 2022 Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809; NASDAQ: EVO) reported that the Company has entered into a drug discovery collaboration with Eli Lilly and Company ("Lilly") in the field of metabolic diseases with a focus on kidney diseases and diabetes (Press release, Evotec, JAN 17, 2022, View Source [SID1234605514]).

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The collaboration leverages Evotec’s extensive experience and track record of delivering in the field of metabolic diseases, as well as its unique and extensive kidney disease patient database, to identify and validate promising novel targets for therapeutic intervention. Evotec will be responsible for the discovery of potential drug candidates for the treatment of diabetes and chronic kidney diseases from targets identified by Lilly or by Evotec. Lilly reserves the right to select up to five programmes developed within this partnership and to continue with any subsequent development, clinical validation and commercialisation.

The collaboration initially runs for a term of three years. In addition to an undisclosed upfront payment, Evotec will be eligible to receive success-based discovery development, regulatory and commercial milestone payments of up to US$ 180 m per programme, as well as tiered royalties on net sales of any products resulting from the collaboration, for a potential overall value up to US$ 1 bn.

Dr Cord Dohrmann, Chief Scientific Officer of Evotec, commented: "We are excited to enter into this research partnership with Lilly. Over a period of several years, Evotec has systematically built a proprietary patient database by conducting multi-omics analyses of biospecimens from patient biobanks covering metabolic and kidney diseases. Evotec’s patient-derived molecular data in combination with our omics-supported multimodality drug discovery platform delivers highest quality drug candidates for our partners. We are proud to collaborate with Lilly in diabetes and kidney diseases as they are one of the leading companies in these areas.